Skip to main content
Article thumbnail
Location of Repository

Vesicular apparatus, including functional calcium channels, are present in developing rodent optic nerve axons and are required for normal node of Ranvier formation

By James J. P. Alix, Annette C. Dolphin and Robert Fern


P/Q-type calcium channels are known to form clusters at the presynaptic membrane where they mediate calcium influx, triggering vesicle fusion. We now report functional P/Q channel clusters in the axolemma of developing central axons that are also associated with sites of vesicle fusion. These channels were activated by axonal action potentials and the resulting calcium influx is well suited to mediate formation of a synaptic style SNARE complex involving SNAP-25, that we show to be located on the axolemma. Vesicular elements within axons were found to be the sole repository of vesicular glutamate in developing white matter. The axonal vesicular elements expressed the glutamate transporter V-ATPase, which is responsible for vesicular glutamate loading. The P/Q channel α1A subunit was found to be present within the axolemma at early nodes of Ranvier and deleterious mutations of the α1A subunit, or an associated α2δ-2 subunit, disrupted the localization of nodal proteins such as voltage-gated sodium channels, β IV spectrin and CASPR-1. This was associated with the presence of malformed nodes of Ranvier characterized by an accumulation of axoplasmic vesicles under the nodal membrane. The data are consistent with the presence of a vesicular signalling pathway between axons and glial cells that is essential for proper development of the node of Ranvier

Publisher: Blackwell Publishing
Year: 2008
DOI identifier: 10.1113/jphysiol.2008.155077
OAI identifier:

Suggested articles


  1. (1971). The physiology of excitable cells. doi
  2. (1999). Calcium block of Na+ channels and its effect on closing rate. doi
  3. (2002). Genetic dysmyelination alters the molecular architecture of the nodal region.
  4. (2006). Hypoxia-ischemia preferentially triggers glutamate depletion from oligodendroglia and axons in perinatal cerebral white matter. doi
  5. (2004). Emerging concepts in periventricular white matter injury. doi
  6. (2001). Ducky mouse phenotype of epilepsy and ataxia is associated with mutations in the Cacna2d2 gene and decreased calcium channel current in cerebellar Purkinje cells.
  7. (2001). Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. doi
  8. (1972). The effect of calcium on the potassium permeability in the myelinated nerve fibre of Xenopus laevis. doi
  9. (2002). The ducky mutation in Cacna2d2 results in altered Purkinje cell morphology and is associated with the expression of a truncated alpha 2 delta-2 protein with abnormal function. doi
  10. (2001). Axonal L-type Ca2+ channels and anoxic injury in rat CNS white matter.
  11. (1996). Axonal calcium entry during fast 'sodium' action potentials in rat cerebellar Purkinje neurones. doi
  12. (2000). Structure and regulation of voltage-gated Ca2+ channels. doi
  13. (2005). Local calcium transients contribute to disappearance of pFAK, focal complex removal and deadhesion of neuronal growth cones and fibroblasts. doi
  14. (1996). Induction of myelination in the central nervous system by electrical activity. doi
  15. (2006). The ducky(2J) mutation in Cacna2d2 results in reduced spontaneous Purkinje cell activity and altered gene expression. doi
  16. (1998). Whole-cell and single-channel analysis of P-type calcium currents in cerebellar Purkinje cells of leaner mutant mice.
  17. (2006). Cortical spreading depression and peri-infarct depolarization in acutely injured human cerebral cortex. doi
  18. (1958). The ionic requirements for the production of action potentials in crustacean muscle fibres. doi
  19. (1998). Axon conduction and survival in CNS white matter during energy deprivation: a developmental study. doi
  20. (1988). Conduction slowing and conduction block induced by high extracellular calcium concentration in isdlated nerve fibres of the frog, rana temporaria.
  21. (1995). Voltage-gated calcium channels in CNS white matter: role in anoxic injury.
  22. (1999). Ataxic mouse mutants and molecular mechanisms of absence epilepsy. doi
  23. (1996). Absence epilepsy in tottering mutant mice is associated with calcium channel defects. doi
  24. (2001). Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel activity.
  25. (2000). Action potential-evoked Ca2+ signals and calcium channels in axons of developing rat cerebellar interneurones. doi
  26. (1982). Rat optic nerve: electrophysiological, pharmacological and anatomical studies during development. doi
  27. (1990). The Effects of Prenatal Intracranial Infusion of Tetrodotoxin on Naturally Occurring Retinal Ganglion Cell Death and Optic Nerve Ultrastructure. doi
  28. (2000). Glutamate receptors in glia: new cells, new inputs and new functions. doi
  29. (2002). Development of nodes of Ranvier. doi
  30. (2004). Guiding neuronal growth cones using Ca2+ signals. doi
  31. (1984). Postnatal differentiation of rat optic nerve fibers: electron microscopic observations on the development of nodes of Ranvier and axoglial relations. doi
  32. (1998). Ionic channels of ecitable membranes. Sinauer Associates, doi
  33. (2004). Functional compensation of P/Q by N-type channels blocks short-term plasticity at the calyx of held presynaptic terminal. doi
  34. (2006). Astrocytes promote myelination in response to electrical impulses. doi
  35. (2002). Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion. doi
  36. (1999). Ablation of P/Q-type Ca(2+) channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the alpha(1A)-subunit. Proc Natl Acad Sci doi
  37. (1997). Induction of sodium channel clustering by oligodendrocytes. doi
  38. (2005). NMDA receptors in oligodendrocyte physiology and pathology. Nature In doi
  39. (2002). [Beta]IV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier. doi
  40. (2005). Calcium signaling and the control of dendritic development. doi
  41. (2000). Localization and physiological regulation of the exocytosis protein SNAP-25 in the brain and pituitary gland of Xenopus laevis. doi
  42. (2001). Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis.
  43. (2007). Vesicular glutamate release from axons in white matter. doi
  44. (1997). Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates.
  45. (1997). Ion transport and membrane potential in CNS myelinated axons I. Normoxic conditions.
  46. (1985). The neuronal endomembrane system. III. The origins of the axoplasmic reticulum and discrete axonal cisternae at the axon hillock.
  47. (1998). Altered calcium channel currents in Purkinje cells of the neurological mutant mouse leaner.
  48. (1996). Ca2+ imaging of CNS axons in culture indicates reliable coupling between single action potentials and distal functional release sites. doi
  49. (1968). The neuropathology of ducky, a neurological mutation of the mouse. A pathological and preliminary histochemical study. doi
  50. (1971). Three syndromes produced by two mutant genes in the mouse. Clinical, pathological, and ultrastructural bases of tottering, leaner, and heterozygous mice.
  51. (2006). NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. doi
  52. (1992). P-type calcium channels blocked by the spider toxin omega-Aga-IVA. doi
  53. (1998). Visualization of the dynamics of synaptic vesicle and plasma membrane proteins in living axons. doi
  54. (2003). Different mechanisms promote astrocyte Ca2+ waves and spreading depression in the mouse neocortex.
  55. (1999). Dependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS.
  56. (2000). Ion channel sequestration in central nervous system axons. doi
  57. (1999). An ultrastructural study of granule cell/Purkinje cell synapses in tottering (tg/tg), leaner (tg(la)/tg(la)) and compound heterozygous tottering/leaner (tg/tg(la)) mice. doi
  58. (1999). Morphologic investigation of rolling mouse Nagoya (tg(rol)/tg(rol)) cerebellar Purkinje cells: an ataxic mutant, revisited. doi
  59. (2005). NMDA Receptors are Expressed doi
  60. (2003). Polarized domains of myelinated axons. doi
  61. (2000). Local control of neurofilament accumulation during radial growth of myelinating axons in vivo. Selective role of site-specific phosphorylation. doi
  62. (1996). Emergence of order in visual system development. doi
  63. (2006). Physiological studies of cortical spreading depression. doi
  64. (1998). Control of myelination by specific patterns of neural impulses.
  65. (1992). Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger. doi
  66. (2000). An oligodendrocyte cell adhesion molecule at the site of assembly of the paranodal axo-glial junction. doi
  67. (2004). Acute ischemic injury of astrocytes is mediated by Na-K-Cl cotransport and not Ca2+ influx at a key point in white matter development. doi
  68. (1998). Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel.
  69. (2004). BetaIV spectrins are essential for membrane stability and the molecular organization of nodes of Ranvier.
  70. (2007). Vesicular release of glutamate from unmyelinated axons in white matter. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.